In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche

被引:52
作者
Breitbach, Martin [1 ]
Kimura, Kenichi [1 ,2 ,3 ]
Luis, Tiago C. [4 ]
Fuegemann, Christopher J. [1 ]
Woll, Petter S. [4 ,7 ]
Hesse, Michael [1 ,2 ]
Facchini, Raffaella [4 ]
Rieck, Sarah [1 ]
Jobin, Katarzyna [6 ]
Reinhardt, Julia [5 ]
Ohneda, Osamu [3 ]
Wenzel, Daniela [1 ]
Geisen, Caroline [1 ,2 ]
Kurts, Christian [6 ]
Kastenmueller, Wolfgang [6 ]
Hoelzel, Michael [5 ]
Jacobsen, Sten E. W. [4 ,7 ,8 ,9 ]
Fleischmann, Bernd K. [1 ]
机构
[1] Univ Bonn, Inst Physiol 1, Med Fac, Life & Brain Ctr, D-53105 Bonn, Germany
[2] Univ Bonn, Med Fac, Dept Cardiac Surg, D-53105 Bonn, Germany
[3] Univ Tsukuba, Dept Regenerat Med & Stem Cell Biol, Tsukuba, Ibaraki 3058575, Japan
[4] Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, MRC,Mol Hematol Unit, Oxford OX3 9DS, England
[5] Univ Bonn, Dept Clin Chem & Clin Pharmacol, D-53105 Bonn, Germany
[6] Univ Bonn, Inst Expt Immunol, D-53105 Bonn, Germany
[7] Karolinska Inst, Dept Med Huddinge, Ctr Hematol & Regenerat Med, Stockholm, Sweden
[8] Karolinska Inst, Wallenberg Inst Regenerat Med, Dept Cell & Mol Biol, Stockholm, Sweden
[9] Karolinska Univ Hosp, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
MESENCHYMAL STEM-CELLS; HEMATOPOIETIC STEM; PROGENITOR CELLS; GENE-EXPRESSION; RNA-SEQ; CULTURE; MICROENVIRONMENT; TISSUES; SPLEEN; ORGANS;
D O I
10.1016/j.stem.2018.01.008
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Despite much work studying ex vivomultipotent stromal cells ( MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP(+) MSCs in various organs. In vivo, EGFP(+) mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP(+) cells exhibited a perivascular distribution pattern. EGFP(+) cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential. Moreover, in the central bone marrow CD73-EGFP(+) specifically labeled sinusoidal endothelial cells, thought to be a critical component of the hematopoietic stem cell niche. Purification and molecular characterization of this CD73-EGFP(+) population revealed an endothelial subtype that also displays a mesenchymal signature, highlighting endothelial cell heterogeneity in the marrow. Thus, the CD73-EGFP mouse is a powerful tool for studying MSCs and sinusoidal endothelium.
引用
收藏
页码:262 / +
页数:22
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